Philadelphia University + Thomas Jefferson University

Calabretta, Bruno

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Bruno Calabretta, MD, PhD

Contact Dr. Calabretta

233 South 10th Street
Philadelphia, PA 19107

(215) 503-4522

Research and Clinical Interests

Molecular mechanisms of normal hematopoiesis and BCR/ABL-dependent leukemogenesis. The process of normal hematopoiesis requires the sequential coordination of many complex events. These include the interaction of stimulatory growth factors with their membrane receptors, generation of the appropriate signal followed by its transduction through the cell membrane and cytoplasm into the nucleus, and finally, DNA synthesis and cell division. Accordingly, it seems reasonable to assume that perturbations in any of these controlled events are likely to result in altered cell growth patterns and possibly in the emergence of cells with a leukemic phenotype, especially in the presence of cumulative alterations in these various components of the proliferative program. As a paradigm of this concept, our studies center on the investigation of the role of the oncogenic BCR/ABL protein in transformation of hematopoietic stem cells and in the role of transcription factors with hematopoietic-specific functions (c-Myb and C/EBPalpha) in normal hematopoiesis and in leukemogenesis.In particular, the studies in the BCR/ABL area will focus on the mechanisms involved in suppression of apoptosis and autophagy. The studies on c-Myb and C/EBPalpha will focus on the effects of these two transcription factors on regulation of normal and leukemic stem cells.

Publications

Most Recent Peer-Reviewed Publications

  1. Targeted Enhancer Activation by a Subunit of the Integrator Complex
  2. Targeting CDK6 and BCL2 exploits the "MYB addiction" of Phþacute lymphoblastic leukemia
  3. Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation
  4. Structure of Nascent Chromatin Is Essential for Hematopoietic Lineage Specification
  5. CDKN2A-independent role of BMI1 in promoting growth and survival of Ph+ acute lymphoblastic leukemia
  6. ATG7 regulates energy metabolism, differentiation and survival of Philadelphia-chromosome-positive cells
  7. Inhibition of Protooncogene Expression by Antisense Oligodeoxynucleotides: Biological and Therapeutic Implications
  8. Expression of μ-protocadherin is negatively regulated by the activation of the β-catenin signaling pathway in normal and cancer colorectal enterocytes
  9. Celecoxib inhibits proliferation and survival of chronic myelogeous leukemia (CML) cells via AMPK-dependent regulation of β-catenin and mTORC1/2
  10. Structure-based screen identifies a potent small molecule inhibitor of Stat5a/b with therapeutic potential for prostate cancer and chronic myeloid leukemia
  11. Monocyte-macrophage differentiation of acute myeloid leukemia cell lines by small molecules identified through interrogation of the connectivity map database
  12. Leukemia stem cells: Old concepts and new perspectives
  13. Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity
  14. MiRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia
  15. Erratum: Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells (Journal of Clinical Investigation (2009) 119:5 (1109-1123) DOI: 10.1172/JCI35660)
  16. Autophagy in Chronic Myeloid Leukaemia: Stem cell survival and implication in therapy
  17. Inhibiting interactions of lysine demethylase LSD1 with snail/slug blocks cancer cell invasion
  18. Expression of p89 c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells
  19. Phosphorylation of serine 21 modulates the proliferation inhibitory more than the differentiation inducing effects of C/EBPα in K562 cells
  20. c-Myb and its target Bmi1 are required for p190BCR/ABL leukemogenesis in mouse and human cells